Thalidomide attenuates the hyporesponsiveness of isolated atria to chronotropic stimulation in BDL rats: The involvement of TNF-α, IL-6 inhibition, and SOCS1 activation | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 3، دوره 22، شماره 11، بهمن 2019، صفحه 1259-1266 اصل مقاله (1.46 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2019.32256.7742 | ||
| نویسندگان | ||
| Ali Hosseini-chegeni1؛ farahnaz Jazaeri1؛ Aliakbar Yousefi-Ahmadipour2؛ Mansour Heidari3؛ Alireza Abdollahi4؛ Ahmad Reza Dehpour* 1، 5 | ||
| 1Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran | ||
| 2Department of Laboratory of Sciences, Faculty of Paramedical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran | ||
| 3Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran | ||
| 4Department of Pathology, School of Medicine, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran | ||
| 5Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran | ||
| چکیده | ||
| Objective(s): Cirrhotic cardiomyopathy is a complication of uncured cirrhosis which is associated with hyporesponsiveness of the heart to sympathetic stimulation. The enhancement of portal pressure, nitric oxide (NO) level, pro-inflammatory mediators and down-regulation of Suppressor of Cytokine Signaling 1 (SOCS1) are involved in this situations. The present study seeks to examine the beneficial effect of thalidomide on cirrhotic cardiomyopathy. Materials and Methods: The male rats were grouped as: Sham/saline, Sham/Thalidomide, Bile Duct Ligation (BDL)/saline and BDL/Thalidomide. BDL model of cirrhosis was used. In the treatment groups, thalidomide (200 mg/kg/day) was administrated by intragastrial gavage for 28 consecutive days, the chronotropic response was assessed in isolated atria by isoproterenol stimulation. Serum levels of NO, IL-6 and TNF-α hepatic level were evaluated. The intrasplenic pulp pressure (ISPP) as the portal pressure and histopathologic assessment were assessed. Real time RT-PCR was used for the evaluation of SOCS1 gene expression. Results: Our results showed that thalidomide administration could significantly increase the atrial chronotropic response in BDL animals. The increased level of portal pressure decreased by thalidomide in BDL animals. Thalidomide could ameliorate the histopathological conditions of BDL rats. Furthermore, the chronic treatment by this drug diminished the elevated levels of NO, TNF-α and IL-6 in BDL animals. On the other hand, hepatic SOCS1 expression was up-regulated by thalidomide treatment in this group. Conclusion: Thalidomide improves the chronotropic hyporesponsiveness of isolated atria in BDL. This effect is probably mediated by the inhibiting NO, TNF-α and IL-6 production, reducing portal pressure and increasing the expression of SOCS1. | ||
| کلیدواژهها | ||
| Cirrhotic cardiomyopathy؛ IL-6؛ SOCS1؛ Thalidomide؛ TNF-α | ||
| مراجع | ||
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